Tomohiro Nishina1, Toshikazu Moriwaki2, Mitsuo Shimada3, Jun Higashijima3, Yoshinori Sakai4, Toshiki Masuishi4, Mitsuharu Ozeki5, Kenji Amagai5, Yuji Negoro6, Shunju Indo7, Tadamichi Denda8, Mikio Sato9, Yuji Yamamoto10, Go Nakajima11, Minoru Mizuta12, Ikuo Takahashi13, Yoshinori Hiroshima14, Hiroyasu Ishida15, Takashi Maeba7, Ichinosuke Hyodo2. 1. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. Electronic address: tnishina@shikoku-cc.go.jp. 2. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 3. Department of Surgery, Tokushima University, Tokushima, Japan. 4. Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tuchiura, Japan. 5. Division of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Kasama, Japan. 6. Division of Gastroenterology, Kochi Health Sciences Center, Kochi, Japan. 7. Division of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Japan. 8. Division of Gastroenterology, Chiba Cancer Center, Chiba City, Japan. 9. Department of Gastroenterology, Ryugasaki Saiseikai Hospital, Ryugasaki, Japan. 10. Division of Gastrointestinal Surgery and Surgical Oncology, Department of Surgery, Ehime University Graduate School of Medicine, Toon, Japan. 11. Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, Tokyo, Japan. 12. Department of Surgery, Mitoyo General Hospital, Kannonji, Japan. 13. Department of Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan. 14. Division of Gastroenterology, Hitachinaka General Hospital, Hitachinaka, Japan. 15. Department of Gastroenterology, National Hospital Organization Mito Medical Center, Ibarakicho, Japan.
Abstract
BACKGROUND: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. PATIENTS AND METHODS: The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. CONCLUSION: UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.
BACKGROUND: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. PATIENTS AND METHODS: The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. CONCLUSION:UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.
Authors: Christine Koch; Anna M Schwing; Eva Herrmann; Markus Borner; Eduardo Diaz-Rubio; Efrat Dotan; Jaime Feliu; Natsuko Okita; John Souglakos; Hendrik T Arkenau; Rainer Porschen; Miriam Koopman; Cornelis J A Punt; Aimery de Gramont; Christophe Tournigand; Stefan Zeuzem; Joerg Trojan Journal: Oncotarget Date: 2017-12-20